Techniques for detecting and diagnosing leprosy in an early stage are of great importance for the prevention of nerve damage. To enable the early diagnoses and prediction of certain reactions, the LUMC research aims to gain more insight into the role different cell types - such as macrophages and T-cells (which have many different sub sets) and the signal substance they produce (such as cytokines)- play in the development of nerve damage in case of leprosy and leprosy reactions.

The LUMC research team is able to isolate and generate various types of these (new) human cellular sub sets, making it possible to study the processes that can lead to nerve damage elaborately. LUMC's theory is that the activation of certain cell types, such as the T-cells that play a role in inflammation diseases (so-called th17 cells) is a main element in this process. Too little is now known about the exact nature and working of these mechanisms, cell types and factors in the human body.

The Turing Foundation contributes a sum of € 260,000 (50%) to the costs of the research, which will run until 2013.

immune biomarkers

TENLEP Trial is a large-scale research project focussing on nerve damage caused by leprosy. Its central research questions are:

The Turing Foundation contributes € 800,000 to this research project (approx. 50% of the total research budget). €200,000 euro is contributed in 2012.

mycobacterium leprae

For some time now, an effective treatment of the leprosy bacterium has been available, consisting of an antibiotics cocktail. Unfortunately, for some people the treatment is accompanied with severe immune responses that cause irreparable nerve damage anyway. It is thought that sometimes, a leprosy bacterium in a Schwann cell is destroyed, after which the Schwann cell could be damaged or even killed by immune cells (T cells) because they respond to the leprosy bacterium's tiny residue (peptides). It could be one of the mechanisms that are involved in causing of nerve damage due to leprosy. Based on models from previous research involving mice, LUMC researchers think that certain T-cell types are an important link in the process, yet are uncertain about its exact nature and functioning.

Now, new research will be conducted to determine which immune cells (and which products they produce, such as signal molecules and cytokines) play a part in the damaging of Schwann cells and nerves with lepers. Researchers think a dysregulation of immune responses to the M.leprae bacterium is responsible for the uncontrolled inflammatory and defensive responses that are characteristic for leprosy. They also predict the unravelling of the mechanisms involved will lead to the identification and development of new methods to treat or even prevent responses in leprosy. Another thing that is very important for the identification of biomarkers for an early diagnosis or prediction of responses in leprosy, as well as for the development of new treatments and improvement of the prevention of responses in leprosy, is a better understanding of the mechanisms of the nerve damage that is so common with responses in leprosy, and the immune cells and substances responsible for it.

The study is aimed at understanding these immunopathological mechanisms, in the hope its results can be used in the development of new strategies for the prediction, detection, and prevention of nerve damage in leprosy.

Until 2015, the Turing Foundation will contribute €150,000 to this study; €30,000 is donated in 2012. Previously, the Turing Foundation contributed €337,500 to phase I of this research.

Researching the immunopathology of leprosy

Previous research of NCI showed an important difference between pathogenic and non-pathogenic bacteria. The difference lies in their location within the host cell. Pathogenic strains such as M.leprae, as well as other mycobacteria, live freely within the cell and can meet proteins that are able to hold antigens (small parts of the bacterium) and present these to the immune system. The strain currently used to prevent mycobacterial infections (vaccine strain BCG) is non-pathogenic. This strain resides in a compartment of the cell that wraps the bacterium in a film (membrane). Researchers want to improve the vaccine by using these characteristics, but to do this it is vital to understand what factors of both the bacterium and the host are involved in the process.

The Turing Foundation will contribute €260,000 to this long-range study (€125,500 of which will be donated in 2011).

Cancer cells

Main goal of the research is to map all known cases of leprosy in Cebu in both space and time, and add all new cases of leprosy to the database (macro-epidemiology). Then, the database should be expanded with the M.leprae strain typing within the clusters of the new cases (micro-epidemiology) to reach a better understanding of the disease's transmission patterns, its risk factors and the virulence patterns of the M.leprae strains. The detailed mapping of cases of leprosy combined with the strain typing that should enable the identification of transmission patterns within a properly demarcated area has never before been attempted.

The Turing Foundation will contribute €118,500 to this long-range study (€75.500 of which will be donated in 2010).

Skin infected with leprosy

The IDEAL consortium is oriented towards the development of immunological tests that can detect leprosy infections in an early stage. Apart from that, molecular tests are developed for gaining a better insight into the transmission of the leprosy bacterium. The ultimate goal is to find tests that can help prevent leprosy infections by the very early (before the illness has even manifested itself) diagnosis and treatment of leprosy.

The partners discuss the results of experiments, exchange experiences and information, provide materials and protocols from individual research projects and perform experiments after mutual consultation and in accordance with a testing format agreed upon. This streamlines and accelerates the research process, and yields quicker results for leprosy elimination.

Since the end of 2005, IDEAL has selected several candidates for both early diagnostics and transmission studies. A test will be developed between 2008 and 2010 that can critically identify leprosy infections in blood, and efforts will be made to enable the further identification of genetic markers on the leprosy bacterium. The markers can be used in transmission studies.

After 2010, IDEAL aims to start a large-scale research project on leprosy prevention through (tailor-made) prophylactic treatment of leper contacts.

The Turing Foundation contributes € 131,000 to this project in 2010. In total, the Turing Foundation contributes € 644,000 in the coming years (approx. 60% of the total project cost) towards the development of the above-mentioned tests.

IDEAL - Initiative for Diagnostic and Epidemiological Assays for Leprosy

Prophylactic treatment means that antibiotics are administered to people who do not (yet) suffer from leprosy. This can be compared to the prevention of malaria in travellers by prescribing medicine. In 2001, a research project started into the effects of prophylactic treatment of leprosy contacts on leprosy prevention. It is conducted in North Western Bangladesh. In the past six years all new leprosy cases, whether in- our outside the patient contact group, have been traced. It has been examined whether rifampicin leprosy occurred among the contact group. This appeared to be the case and even more so if the prophylactic treatment was combined with a BCG vaccine - which is today a standard vaccination for most children in the first year of their lives. During the current one year project, the research team aims, on the basis of information already available, to answer several questions related to the transmission of the leprosy bacteria and the success of prophylactic treatment.

The Turing Foundation pays 50% (€ 40,000) of the research costs of this project, which will take one year.

mycobacterium leprae